Non-proteinuric Pre-eclampsia Research Articles

WITHDRAWN: Prevalence of Non-Proteinuric Preeclampsia at Mansoura University Hospitals

ObjectivesPre-eclampsia (PE) is a complex, multisystem disorder of unknown aetiology. PE is the development of hypertension and proteinuria in a previously normotensive woman at or after 20 weeks of gestation. Recently, the definition has been broadened to include non-proteinuric, in addition to proteinuric PE, accompanied by evidence of maternal organ dysfunction and uteroplacental dysfunction. MethodsThis cross-sectional study included pregnant women at 20 weeks gestation or more who attended an outpatient clinic and were admitted to the Obstetrics and Gynecology Department over 12 months (from July 2020 to June 2021) due to hypertension with or without proteinuria. A blood sample was taken to investigate the haemoglobin, platelet, liver, and renal function. Doppler study of the umbilical and middle cerebral artery were done to assess the uteroplacental function. ResultsOf two types of PE among the total of 889 cases, prevalence of proteinuric PE (110/889 or 12.3%) was significantly higher than non-proteinuric PE (55/889 or 6.1%) (OR and 95% CI = 2.1 (1.5–3.0) P < 0.0001). ConclusionThe prevalence of non-proteinuric PE (6.1%) is about half of proteinuric (12.3%), which has broadened the scope of diagnosis of PE to be non-proteinuric and proteinuric instead of just proteinuric. Liver involvement was significantly more frequent in proteinuric PE, while uteroplacental dysfunction was more frequent in non-proteinuric PE.

Nonproteinuric Preeclampsia among Women with Hypertensive Disorders of Pregnancy at a Referral Hospital in Southwestern Uganda.

Background Preeclampsia is a priority obstetric emergency requiring urgent diagnosis and treatment to avert poor pregnancy outcomes. Nonproteinuric preeclampsia poses even greater diagnostic challenges due to contested diagnostic criteria by the clinical practice guidelines and variable clinical presentation. Previously, preeclampsia was only diagnosed if high blood pressure and proteinuria were present. This study determined the prevalence of nonproteinuric preeclampsia and associated factors among women admitted with hypertensive disorders of pregnancy at a referral hospital in southwestern Uganda. Methods Women with hypertensive disorders of pregnancy were consecutively enrolled in a cross-sectional study at Mbarara Regional Referral Hospital between November 2019 and May 2020. We interviewed all pregnant women ≥20 gestation weeks presenting with hypertension and obtained their sociodemographic, medical, and obstetric characteristics. We excluded women with chronic hypertension. We measured bedside dipstick proteinuria in clean-catch urine. Preeclampsia was defined as hypertension plus any feature of severity including <100,000 platelets/ul, creatinine >1.1 g/dl, and liver transaminases ≥twice upper normal limit with or without proteinuria. We defined nonproteinuric preeclampsia in participants with <+2 urine dipstick cut-off and determined the factors associated with nonproteinuric preeclampsia using logistic regression. Results We enrolled 134 participants. The mean age was 26.9 (SD ± 7.1) years and 51.5% were primigravid. The prevalence of nonproteinuric preeclampsia was 24.6% (95% CI: 17.9–32.7). Primigravidity (aOR 2.70 95% CI: 1.09–6.72, p = 0.032) was the factor independently associated with nonproteinuric preeclampsia. Conclusion Nonproteinuric preeclampsia was common, especially among primigravidae. We recommend increased surveillance for nonproteinuric preeclampsia, especially among first-time pregnant women, who may not be detected by the traditional criteria. Obstetrics care providers should emphasize laboratory testing beyond proteinuria, among all women with hypertensive disorders of pregnancy to optimally diagnose and manage nonproteinuric preeclampsia.

Evaluation of the clinical impact of the revised ISSHP and ACOG definitions on preeclampsia.

In 2018/2013 both ISSHP and ACOG revised their original statements and postulated new criteria for preeclampsia with and without severe features. Most importantly, preeclampsia can now also be established in the absence of proteinuria when other specific symptoms are present. What is the clinical impact of the use of three different new definitions for the diagnosis of preeclampsia? Retrospective cohort study of all pregnant women who gave birth in the Erasmus MC between 01 and 01-2014 and 01-01-2016. Hypertensive disorders of pregnancy (HDP) were defined when blood pressure was elevated at least during two occasions. All HDP cases were classified according to the ISSHP 2001, ISSHP 2018 and ACOG 2013 definitions. In our cohort (N=4395) 878 patients had HDP (20,0%). The ISSHP 2018/ACOG 2013 definition cause a significant increase in patients with (superimposed) preeclampsia versus the ISSHP 2001 definition, from 272 patients (6,2%) to respectively 360 (8,2%)/290 (6,6%) (p<0,001/p<0,001). This increase is due to non-proteinuric preeclampsia cases. According to the ACOG 2013 definition there were 154 (53,1%) cases of preeclampsia with severe features. Neonatal NICU admission rates were almost doubled in the proteinuric preeclampsia group compared to the non-proteinuric preeclampsia group. Implementation of the ISSHP 2018/ACOG 2013 definitions cause a shift from gestational hypertension and chronic hypertension towards (superimposed) preeclampsia (relative increase 10%/2%). These increases are caused by inclusion of non-proteinuric cases. More research is necessary into the course and prognosis of especially non-proteinuric preeclampsia cases.

44. Evaluation of the clinical impact of the revised ISSHP and ACOG definitions on preeclampsia and on severe preeclampsia

Background In 2013/2014 both ISSHP and ACOG revised their original statement and postulated new criteria for (severe) preeclampsia, by which the diagnosis preeclampsia can also be established in the absence of proteinuria when other specific symptoms are present. Objective What is the clinical impact of the use of three different new criteria for the diagnosis of preeclampsia and severe preeclampsia? Methods Retrospective cohort study of all pregnant women who gave birth in the Erasmus MC between 01-01-2014 and 01-01-2016. Hypertensive disorders of pregnancy (HDP) were defined when ⩾2 times during pregnancy high blood pressure (⩾140 mmHg systolic and/or ⩾90 mmHg diastolic) was measured. All HDP cases were then classified according to the ISSHP 2001, ISSHP 2013/2014 and ACOG 2013 criteria. Results In our cohort (N = 4395) 878 patients had HDP (20,0%). The ISSHP 2014/ACOG 2013 criteria cause a significant increase in patients with (superimposed) preeclampsia versus the ISSHP 2001 criteria, from 272 patients (6,2%) to respectively 360 (8,2%)/290 (6,6%) (p Discussion Implementation of the ISSHP 2014/ACOG 2013 criteria causes a shift from gestational hypertension and chronic hypertension towards (superimposed) preeclampsia (relative increase 10%/2%) and severe preeclampsia (4.6%). Since women with preeclampsia have an increased risk of developing cardiovascular disease later in life, we recommend further research into the course and prognosis of especially non-proteinuric preeclampsia.

183. Severe hypertension and maternal organ involvements were closely related in the disease of hypertensive disorders of pregnancy

Purpose Severe hypertension (sevHT, over 160/110 mmHg) is supposed to be pathogenesis of maternal organ involvements in the disease of hypertensive disorders of pregnancy. It remains that to what extent each target organ is to be damaged in sevHT. Methods 2746 pregnant women managed in our tertial perinatal center from 2013 to 2016 were entered in this study retrospectively. All cases with sevHT were managed expectantly in the same antihypertensive protocol. Disease type was defined by restrictive criteria in irrespective of organ involvements. Result 192 cases of 2746 found sevHT and 91 cases was in antepartum (AP), 90 in intrapartum (IP) and 21 in postpartum (PP). 9 cases (11%) of 91 cases in AP showed gestational hypertension (GH), 47 (58%) preeclampsia and 22 (27%) preeclampsia superimposed on chronic hypertension (PES). 11% of GH in AP, 58% of PE in AP, 41% of PES in AP, 11% in IP and 29% in PP complicated with organ involvements. HELLP related involvements such as elevated liver enzymes, low platelets count or renal impairment were observed in 34% of PE in AP, 27% of PES in AP and 14% in PP. Hyperpermeability involvements such as pleural edema or massive ascites were diagnosed in 9% of PE or PES in AP. About CNS involvements, eclampsia were observed in 4% of PE in AP, cerebral vascular spasms 6% of PE in AP, 5% of PES in AP, 1% in IP and 14% in PP. Conclusions SevHT found in 7% (192 of 2746). CNS involvements found 9% of preeclamptic disease. HELLP related involvements related to the preeclamptic disease. Hyperpermeability involvements had even 11% in GH in preeclamptic disease. We showed maternal organ involvements were closely related with preeclamptic disease with sevHT. Also hyperpermeability involvements related with GH with sevHT. In discussing non-proteinuric preeclampsia, hyperpermeability disorders play important role.

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Objectives To study adverse outcomes associated with definitions of preeclampsia and compare them to patients not meeting diagnostic criteria for preeclampsia. Methods A multicenter, prospective, observational study was conducted on women with suspected preeclampsia (PE). Patients were managed by local protocol, and final diagnoses were adjudicated by independent panel. Subjects were classified as Traditional PE (TrPE) with both hypertension and proteinuria, or eclampsia or HELLP syndrome (ACOG 2012); Nonproteinuric PE (NpPE) with severe gestational hypertension (BP >160/110) or mild hypertension plus ⩾1 severe feature (ACOG, 2013); or No diagnosis (NoD). Adverse outcomes included preterm birth (PTB), SGA, IUFD, neonatal demise (NND), and severe maternal adverse outcomes (MAO - abruption, renal failure, pulmonary edema, fatty liver, TTP, DIC, stroke, and retinal detachment). Comparisons tested with Chi square, α = 0.05. Results A total of 757 subjects with signs or symptoms of PE were enrolled Table 1 ). 96 had chronic hypertension or mild gestational hypertension. As compared to TrPE, women with NpPE experienced similar rates of all adverse outcomes. Subjects with NoD also had similar rates of IUFD, NND, and MAO. However, women with NoD experienced lower rates of PTB p Conclusions Among patients with suspected preeclampsia before 35 weeks, the risks of severe adverse outcomes are elevated, even for those who fall outside current clinical diagnostic categories. Patients without a diagnosis, however have fewer preterm deliveries and SGA babies. Diagnostic criteria for preeclampsia poorly predict severe adverse outcomes, and may contribute to preterm delivery. Disclosures D. Woelkers: None. J. Barton: None. P. von Dadelszen: None. B. Sibai: None.

Guidelines for the management of hypertensive disorders of pregnancy 2008

This is the Executive Summary of updated guidelines developed by the Society of Obstetric Medicine of Australia and New Zealand for the management of hypertensive diseases of pregnancy. They address a number of challenging areas including the definition of severe hypertension, the use of automated blood pressure monitors, the definition of non-proteinuric pre-eclampsia and measuring proteinuria. Controversial management issues are addressed such as the treatment of severe hypertension and other significant manifestations of pre-eclampsia, the role of expectant management in pre-eclampsia remote from term, thromboprophylaxis, appropriate fluid therapy, the role of prophylactic magnesium sulfate and anaesthetic issues for women with pre-eclampsia. The guidelines stress the need for experienced team management for women with pre-eclampsia and mandatory hospital protocols for treatment of hypertension and eclampsia. New areas addressed in the guidelines include recommended protocols for maternal and fetal investigation of women with hypertension, preconception management for women at risk of pre-eclampsia, auditing outcomes in women with hypertensive diseases of pregnancy and long-term screening for women with previous pre-eclampsia.

Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension

To determine whether outcomes differed for women with pre-eclampsia according to the presence of proteinuria and whether non-proteinuric pre-eclampsia is similar to gestational hypertension. From 1987 to 2005, at three hospitals in Sydney, Australia, women referred to the obstetric medicine team were recruited. Outcomes for three groups were compared: proteinuric pre-eclampsia, non-proteinuric pre-eclampsia and gestational hypertension. Women with proteinuric pre-eclampsia were more likely to have severe hypertension (39 versus 30%, P = 0.003), deliver preterm infants (39 versus 30%, P = 0.007) and had a higher perinatal mortality rate (25.2 versus 5.7 per 1000, P = 0.02) than those with non-proteinuric pre-eclampsia, who were more likely to have thrombocytopenia and liver disease. Women with non-proteinuric pre-eclampsia were more likely to have multiple pregnancies (3.9 versus 9.9%, P < 0.001), experience severe hypertension (8.9 versus 29.7%, P < 0.001), and deliver preterm infants (11.3 versus 30.2%, P < 0.001) who were small for gestational age (12.7 versus 20.9%, P < 0.001) than those with gestational hypertension. This study highlights differences between non-proteinuric pre-eclampsia and gestational hypertension. The subclassification of 'non-proteinuric pre-eclampsia' should be added to existing classification systems to alert clinicians to potential risks.

Serum Lipid Levels at 28–32 Weeks Gestation and Hypertensive Disorders

Background: The etiology and pathogenesis of hypertensive disorders complicating pregnancy are poorly understood, and the definition of these disorders is controversial. Methods: In a prospective study, 470 primigravida women between 28 and 32 weeks of pregnancy were evaluated for serum levels of total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride. Afterward, they were observed for any symptoms of preeclampsia and gestational hypertension until 40 weeks of gestational age. We than compared the serum lipid levels among women with preeclampsia and gestational hypertension with those of matched women with normal pregnancies. Results: The numbers of patients developing preeclampsia and gestational hypertension were 25 (5.3%) and 32 (6.8%), respectively. At the beginning of the study, the mean values of serum triglyceride levels between women who later experienced preeclampsia or gestational hypertension and those who did not differed significantly (p < 0.0001, p < 0.03). Conclusion: Although many cases of gestational hypertension represent latent essential hypertension based on the lipid levels, some of these women display true pregnancy-induced hypertension or nonproteinuric preeclampsia.

A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13.

Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incompletely understood, but familial clustering of the disease is apparent. Here we report the results of a genome-wide screen of Icelandic families representing 343 affected women. Including those patients with non-proteinuric pre-eclampsia (gestational hypertension), proteinuric pre-eclampsia and eclampsia, we detected a significant locus on 2p13 with a lod score of 4.70 (single point P < 3.49 x 10(-6)). This is the first reported locus for pre-eclampsia meeting the criteria for genome-wide significance.

Lipid peroxide and vitamin E patterns in pregnant women with different types of hypertension in pregnancy

OBJECTIVES: We sought to evaluate the circulating levels of lipid peroxides and vitamin E and the placental levels of lipid peroxides in pregnant women with different types of hypertension. STUDY DESIGN: Lipid peroxides were measured in serum and placental tissue by the thiobarbituric acid method and high-pressure liquid chromatography, and vitamin E was measured by high-pressure liquid chromatography. The patients studied were 36 healthy pregnant women and 92 women with hypertension classified as having mild gestational hypertension ( n = 28), severe gestational hypertension ( n = 10), preeclampsia ( n = 34), and chronic hypertension ( n = 20). RESULTS: Lipid peroxides in serum and placental tissue were significantly increased, and vitamin E levels in serum were significantly decreased in women with severe gestational hypertension and preeclampsia compared with controls. The groups of mild gestational hypertension or chronic hypertension had similar values of lipid peroxides or vitamin E as controls. CONCLUSIONS: Our results suggest that the category of gestational hypertension may be composed of at least two entities with different pathophysiology and support the concept of nonproteinuric preeclampsia. (Am J Obstet Gynecol 1998;178:1072-6.)

Platelet sodium/hydrogen ion exchange in normal pregnancy and non-proteinuric pre-eclampsia.

In non-pregnant individuals, abnormalities in cation transport in vascular tissues have been linked to essential hypertension. In the present study, we consider whether Na+/H+ exchange (NHE) is affected in non-proteinuric pre-eclampsia (NPP). Platelet NHE characteristics and plasma cholesterol were measured in a cross-sectional study of normal primigravidae at 14 +/- 0.5 (n = 9), 29 +/- 0.7 (n = 7), 39 +/- 0.4 (n = 8) weeks gestation, in women with NPP (n = 15) and in non-pregnant women (n = 8). Amiloride-sensitive 22Na uptake was measured in platelets which had been acid loaded, to stimulate NHE, by suspension in isotonic potassium propionate buffer (pH 6.7). Intraplatelet radioactivity was used to calculate the affinity (Km) and the capacity (Vmax) of Na+ uptake. In normotensive women, Vmax (mean +/- s.e.) at 14, 29, 39 weeks gestation and 6 weeks postpartum were 452 +/- 46, 469 +/- 33, 713 +/- 101 and 562 +/- 77 pmolNa+/10(6) cells/min respectively; the third trimester values were higher (P < 0.05) than those in the first and second trimester and were also higher than those of non-pregnant women (415 +/- 20). Vmax of patients with NPP in the third trimester (712 +/- 44) was not different from gestational age-matched controls. Km values were not affected by gestational age or NPP. Plasma cholesterol concentration was positively correlated with Vmax values during normotensive pregnancy (r = 0.493, P < 0.05). In conclusion, the capacity for amiloride-sensitive Na+ uptake by platelets correlates positively with gestational age during normal pregnancy. However, neither the capacity nor affinity for Na+ was altered in NPP platelets suggesting that NHE is not implicated in the pathophysiology of this condition.

Variation in lipid levels during pregnancy in women with different types of hypertension.

To evaluate the levels of serum lipids (cholesterol and triglycerides) in pregnant women with different types of hypertension, at the first, second and third trimesters of pregnancy. Cholesterol and triglyceride levels at the first, second and third trimesters of gestation were recorded for 115 women with hypertension during pregnancy, and 115 healthy pregnant women matched for age and body mass index. Cases were classified as having mild gestational hypertension (25), severe gestational hypertension (15), mild preeclampsia (20), severe preeclampsia (20), chronic hypertension (20), and superimposed preeclampsia (15). Cholesterol levels were not statistically different between cases and controls in any form of hypertension. At 20 and 34 weeks' gestation, triglyceride levels were significantly higher than controls in women with severe gestational hypertension, mild and severe preeclampsia, and superimposed preeclampsia, but not in mild gestational hypertension or chronic hypertension. The significant elevation in triglycerides was already present at 10 weeks in mild and severe preeclampsia. The data suggest that the alterations in lipid metabolism observed in preeclampsia are already present at the first trimester of pregnancy. Women with severe gestational hypertension presented a pattern of triglycerides similar to that of preeclamptic women, but mild gestational hypertension resembled chronic hypertension in this respect. This supports the concept that, although in many cases gestational hypertension represents latent essential hypertension, some of these women, probably the most severe cases, present with true pregnancy-induced hypertension, or nonproteinuric preeclampsia.

The definition of pre-eclampsia.

Redman and Jefferies have proposed a revised definition of pre-eclampsia which is based on absolute blood pressure levels and an increment from the baseline in the first half of pregnancy. There is no requirement for proteinuria. This definition should facilitate the distinction between nonproteinuric pre-eclampsia and other causes of nonproteinuric gestational hypertension, such as chronic essential hypertension. 1. To determine whether the blood pressure criteria of Redman and Jefferies can select women with characteristics of pre-eclampsia from the group of women with gestational hypertension by the current criteria of the International Society for the Study of Hypertension in Pregnancy (ISSHP). 2. To determine the level of agreement between the classification system proposed by Redman and Jefferies and that of the ISSHP. A prospective study. Obstetric unit, Dudley Road Hospital, Birmingham, UK. Six hundred and ninety-two healthy nulliparous women and 11 women with chronic hypertension antedating pregnancy. 1. Differences in maternal characteristics and obstetric outcome among women with gestational (nonproteinuric) hypertension by the ISSHP criteria, meeting (and failing to meet) the Redman and Jefferies' blood pressure criteria. 2. The proportion of women classified as normal, proteinuric pre-eclampsia, and chronic hypertension on the basis of both Redman and Jefferies' criteria and the current ISSHP criteria. There were 55 women with gestational hypertension alone by the ISSHP criteria, of whom 33 met Redman and Jefferies' blood pressure criteria for pre-eclampsia. This group of 33 women had characteristics of nonproteinuric pre-eclampsia, compared with the remaining 22 women in the ISSHP gestational hypertension category who had characteristics of chronic hypertension. The group of 33 were significantly younger and less obese, had significantly lower blood pressure at their first antenatal visit and their obstetric outcome was poorer. The Redman and Jefferies' blood pressure criteria identified as normal 99.5% (95% CI, 98.6% to 99.9%) of women who were also characterised as normal on the basis of the ISSHP criteria (622/625). There were 12 women with proteinuric pre-eclampsia by the ISSHP criteria of whom 11 (92%; 95% CI, 62% to 99.8%) met Redman and Jefferies' blood pressure criteria for pre-eclampsia. None of the 11 women with chronic hypertension antedating pregnancy met these criteria. In this population the blood pressure criteria for pre-eclampsia proposed by Redman and Jefferies select women with features of pre-eclampsia (i.e., proteinuria and relatively poor outcome) and, in particular, they enable a distinction to be made between nonproteinuric pre-eclampsia and other causes of gestational hypertension.

Prediction of the severity of pre-eclampsia by utero-placental Doppler studies

SummaryWhether or not Doppler studies of the utero-placental circulation can help indicate which hypertensive pregnancies will develop other features of pre-eclampsia was investigated. A prospective, longitudinal study of utero-placental blood velocity waveform by continuous wave Doppler ultrasound in third trimester hypertensive pregnancies was conducted. Sixty patients were referred for investigation of hypertension in the third trimester of pregnancy; 25 subsequently developed other features of pre-eclampsia. Uterine blood velocity waveforms were assessed by the resistance index and the presence or absence of a dichrotic notch. Proteinuria was defined as at least a + on dip-stick testing on two occasions or > 500 mg/24 hours in the absence of urinary infection.Utero-placental Doppler studies were not demonstrated to differ in the patients with proteinuric pre-eclampsia from those with non-proteinuric preeclampsia. Continuous wave Doppler studies of the utero-placental circulation in the third trimester...

Maternal immunization by husband's leukocytes for repeated fetal death associated with mild pre-eclampsia--case report with successful outcome.

We report a case of repeated fetal death at 31 gestational weeks associated with mild non-proteinuric pre-eclampsia and intrauterine growth retardation. After double intradermal immunisation with paternal leukocytes, a third pregnancy proceeded uneventfully until it ended at 38 weeks. Maternal anti-paternal blocking antibody activity was assessed by the erythrocyte antibody inhibition (EAI) test. Serologic testing revealed that the couple did not share HLA class I antigens. The mechanisms underlying the likely benefit from immunotherapy are discussed.

Screening for intrauterine growth retardation in late pregnancy.

A prospective study was performed on an unselected area-based population in order to improve the antenatal diagnosis of intrauterine growth retardation (IUGR). The clinical importance of simple clinical tests to follow fetal growth (measurements of the symphysis-fundus (SF) distance and recordings of maternal pregnancy weight gain) was investigated. Risk factors for IUGR, appearing in late pregnancy (vaginal bleeding, non-proteinuric pregnancy hypertension and pre-eclampsia) were also studied. A pathological SF curve (frequency 3.5%) was found to be valuable, but mainly as a screening instrument rather than a diagnostic tool for IUGR. Pre-eclampsia was the only risk factor appearing in late pregnancy that could be associated with IUGR. Previously we have recommended early pregnancy screening for the following high risk factors for IUGR: smoking, previous birth of a low birth weight infant, low pre-pregnancy weight, renal disease and addiction. When also screening for pre-eclampsia, 22% of the population exhibited at least one screening factor. Retrospectively we identified all severely growth-retarded infants (birth weight for gestational age less than or equal to -2 S.D.) born in 1980 (n = 27). 23 of these infants were delivered to mothers exhibiting high-risk factors for IUGR or a pathological SF curve. In this way a high-risk group for IUGR can be identified, which should be monitored more carefully during the last period of pregnancy.